Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets.

Cyclooxygenase (COX)-1 or -2 and prostaglandin (PG) synthases catalyze the formation of various PGs and thromboxane (TX) A(2). We have investigated the expression and activity of COX-1 and -2 during human megakaryocytopoiesis. We analyzed megakaryocytes from bone marrow biopsies and derived from thrombopoietin-treated CD34(+) hemopoietic progenitor cells in culture. Platelets were obtained from healthy donors and patients with high platelet regeneration because of immune thrombocytopenia or peripheral blood stem cell transplantation. By immunocytochemistry, COX-1 was observed in CD34(+) cells and in megakaryocytes at each stage of maturation, whereas COX-2 was induced after 6 days of culture, and remained detectable in mature megakaryocytes. CD34(+) cells synthesized more PGE(2) than TXB(2) (214 +/- 50 vs. 30 +/- 10 pg/10(6) cells), whereas the reverse was true in mature megakaryocytes (TXB(2) 8,440 +/- 2,500 vs. PGE(2) 906 +/- 161 pg/10(6) cells). By immunostaining, COX-2 was observed in <10% of circulating platelets from healthy controls, whereas up to 60% of COX-2-positive platelets were found in patients. A selective COX-2 inhibitor reduced platelet production of both PGE(2) and TXB(2) to a significantly greater extent in patients than in healthy subjects. Finally, we found that COX-2 and the inducible PGE-synthase were coexpressed in mature megakaryocytes and in platelets. We conclude that both COX-isoforms contribute to prostanoid formation during human megakaryocytopoiesis and that COX-2-derived PGE(2) and TXA(2) may play an unrecognized role in inflammatory and hemostatic responses in clinical syndromes associated with high platelet turnover

Type II estrogen binding sites (EBS) in intracranial tumors.

Four meningiomas and six neuroepithelial tumors were assayed for the presence of estrogen receptors (ER), type II estrogen binding sites (EBS) and progesterone receptors (PgR). ER were detected in 7 out of 10 cases with levels ranging between 2.5 and 20.7 fmoles/mg of cytosolic protein. On the contrary, PgR were found in all samples (10 cases) and their levels ranged between 8.8 and 130.6 fmoles/mg of cytosolic protein. All tumor samples expressed appreciable amounts of type II EBS ranging between 452 and 2320 fmoles/mg of protein. Although the precise functional role of type II EBS is still unknown, their presence may reflect an hormonal sensitivity of these tumors